The physiological function and mode of regulation of transglutaminases are being studied as to their role in the formation of "temporary tissue matrix" (fibrin or fibrin-connective tissue) during tissue or bone fracture repair and in the modulation of specific cellular processes. The cross-linking of Alpha2-plasmin inhibitor to fibrin plays a major role in stabilization of the "temporary tissue matrix" which is vital for the initial phase of cell migration and proliferation during tissue repair. A number of substances such as oxygen metabolites, sulfhydryls, and albumin in the plasma and tissue fluid can affect the catalytic activity of factor XIIIa and transglutaminases. We find that lipids and neutral detergents also play an important role in the modulation of factor XIIIa activity. Lipoproteins are shown to be capable of cross-linking in the presence of factor XIIIa and cellular transglutaminase. A possible role of transglutaminase in oral physiology is being investigated. The ductal saliva from rat parotid and submandibular glands following isoproterenol stimulation contains both transglutaminase and proteins that are modified or crosslinked by transglutaminase. Transglutaminase in whole saliva is also found to be derived from the epithelium of the oral cavity.